Direct conversion of human myoblasts into brown-like adipocytes by engineered super-active PPARγ

Yanbei Zhu, Rongze Yang, John McLenithan, Daozhan Yu, Hong Wang, Yaping Wang, Devinder Singh, John Olson, Carole Sztalryd, Dalong Zhu, Da Wei Gong

Research output: Contribution to journalArticlepeer-review

Abstract

Objective To determine whether super-activation of PPARγ can reprogram human myoblasts into brown-like adipocytes and to establish a new cell model for browning research. Methods To enhance the PPARγ signaling, M3, the transactivation domain of MyoD, was fused to PPARγ. PPARγ and M3-PPARγ-lentiviral vectors were used to convert human myoblasts into adipocytes. Brown adipocyte markers of the reprogrammed adipocytes were assessed by qPCR and protein analyses. White adipocytes differentiated from subcutaneous stromal vascular cells and perithyroid brown fat tissues were used as references. Results In transient transfections, M3-PPARγ had a stronger constitutive activity than PPARγ by reporter assay. Although the transduction of either PPARγ or M3-PPARγ induced adipogenesis in myoblasts, M3-PPARγ drastically induced the brown adipocyte markers of UCP1, CIDEA, and PRDM16 by 1,050, 2.4, and 5.0 fold, respectively and increased mitochondria contents by 4 fold, compared to PPARγ. Conclusions Super-activation of PPARγ can effectively convert human myoblasts into brown-like adipocytes and a new approach to derive brown-like adipocytes.

Original languageEnglish (US)
Pages (from-to)1014-1021
Number of pages8
JournalObesity
Volume23
Issue number5
DOIs
StatePublished - May 1 2015

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

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